Meta-analysis: cyclooxygenase-2 inhibitors are no better than nonselective nonsteroidal anti-inflammatory drugs with proton pump inhibitors in regard to gastrointestinal adverse events in osteoarthritis and rheumatoid arthritis

Eur J Gastroenterol Hepatol. 2011 Oct;23(10):876-80. doi: 10.1097/MEG.0b013e328349de81.


Objective: To compare cyclooxygenase-2 (Cox-2) inhibitors alone with NSAIDs plus proton pump inhibitors (PPIs) in preventing gastrointestinal adverse events: upper gastrointestinal (UGI) adverse events and gastrointestinal symptoms in Osteoarthritis and Rheumatoid arthritis.

Methods: PubMed, the Cochrane Library, EMBASE, ISI Web of Knowledge, Chinese Biomedical Literature Database, and reference lists of relevant papers for articles published 1990-2010.12 were searched. The related data matching standards set for this study were extracted. Statistical analyses were carried out using RevMan (5.0) software.

Results: The meta-analysis of six randomized controlled trials with a total of 6219 patients revealed that there was no difference in the UGI adverse events between Cox-2 inhibitors and nonselective NSAIDs with concurrent use of PPIs [relative risk (RR) 0.61, 95% confidence interval (CI) 0.34-1.09]. There was no significant difference in gastrointestinal symptoms (RR 1.10, 95% CI: 0.88-1.39) and the cardiovascular adverse events (RR 1.67, 95% CI: 0.78-3.59) between the two groups.

Conclusion: Cox-2 inhibitors are no better than nonselective NSAIDs with PPIs in regard to UGI adverse events, gastrointestinal symptoms and cardiovascular adverse events in Osteoarthritis and Rheumatoid arthritis. On the basis of the current evidence and the combined wishes of the patient, clinicians should carefully consider and weigh both gastrointestinal and cardiovascular risk before selecting NSAID plus PPIs or Cox-2 inhibitors.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Cardiovascular Diseases / chemically induced
  • Cyclooxygenase 2 Inhibitors / adverse effects*
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Drug Therapy, Combination
  • Gastrointestinal Diseases / chemically induced*
  • Humans
  • Osteoarthritis / drug therapy*
  • Proton Pump Inhibitors / adverse effects*
  • Proton Pump Inhibitors / therapeutic use
  • Randomized Controlled Trials as Topic


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Proton Pump Inhibitors